Intravenous cidofovir treatment for recalcitrant warts in the setting of a patient with myelodysplastic syndrome

Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.     

Digital radiography of subtle pulmonary abnormalities: an ROC study of the effect of pixel size on observer performance

Forty conventional radiographs with examples of mild interstitial infiltrates and subtle pneumothoraces and 40 normal studies of the chest were selected and digitized, with pixel sizes of 1.0, 0.5, 0.2, and 0.1 mm. Observer performance tests were carried out using receiver operating characteristic analysis. Conventional radiographs and digitized images were compared. The results indicate that, in such cases, diagnostic accuracy increases significantly as the pixel size is reduced, at least to the 0.1-mm level. We conclude that, for digital systems using screen-film or similar image receptors, use of a pixel size substantially larger than 0.1 mm may result in some loss of diagnostic accuracy.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.     

Rectal sensorimotor characteristics in female patients with idiopathic constipation with or without paradoxical sphincter contraction

Patients with chronic constipation fulfilling the Thompson criteria can show paradoxical sphincter contraction. Aim of this study was to evaluate rectal sensorimotor characteristics in patients with constipation with or without paradoxical sphincter contraction. Thirty female patients with chronic constipation and 22 female controls were investigated with anal manometry and rectal barostat. Paradoxical sphincter contraction was shown with manometry as a paradoxical increase of anal pressure during straining. Visceral sensitivity and compliance were tested by intermittent and continuous pressure-controlled distension. Patients were classified according to their sensations and compliance into normal, hypersensitive, reduced compliant, insensitive or excessive compliant rectum. Postprandial rectal response (PRR) and phasic volume events (PVEs) were registered for 1 h after a 600-kCal meal. Paradoxical sphincter contraction was found in 13 (43%) patients. In these patients, rectal sensitivity scores were higher (P = 0.045) than in patients without paradoxical contractions, but rectal compliance was not different. In 90% of patients an abnormal rectal sensitivity or compliance was found: excessively compliant in 35%, reduced compliant in 10%, hypersensitive in 27% and hyposensitive in 17%. Both patients with constipation (11%; P = 0.042) and controls (25%; P = 0.002) exhibited the presence of a postprandial rectal response. This response was not significantly different between idiopathic constipation, paradoxical sphincter contraction and controls. Patients with rectal hypersensitivity had lower response than other patients (P = 0.04). Patients with constipation had fewer basal PVEs compared controls (P = 0.03). Postprandial PVEs increased in both patients (P = 0.014) and controls (P < 0.001). Postprandial rectal response and PVE were not different in patients with or without paradoxical sphincter contraction. A total of 90% of female patients with idiopathic constipation show an abnormality in rectal sensation or compliance. The postprandial rectal response was comparable between patients with constipation and controls, however, PVEs were diminished. Patients with paradoxical sphincter contraction had higher rectal sensitivity but an unaltered compliance and postprandial rectal response. Future trials should investigate whether the classification of rectal abnormalities in patients with constipation has clinical importance.